Emerging evidence shows that cognitive deficits in Alzheimer disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. Results revealed that AD networks, compared to networks of age matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients functional brain networks and their cognitive scores. These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently used neurophysiological tests in neurodegenerative diseases.
Graph theory has been extensively used to investigate brain network topology and its changes in disease cohorts. However, many graph theoretic analysis-based brain network studies focused on the shortest paths or, more generally, cost-efficiency. In this work, we use two new concepts, connectedness and 2-connectedness, to measure different global properties compared to the previously widely adopted ones.
Diverse cognitive processes set different demands on locally segregated and globally integrated brain activity. However, it remains unclear how resting brains configure their functional organization to balance the demands on network segregation and integration to best serve cognition. Here, we use an eigenmode-based approach to identify hierarchical modules in functional brain networks, and quantify the functional balance between network segregation and integration. In a large sample of healthy young adults (n=991), we combine the whole-brain resting state functional magnetic resonance imaging…
Small-world structures are often used to describe structural connections in the brain. In this work, we compare the structural connection of cortical areas of a healthy brain and a brain affected by Alzheimer's disease with artificial small-world networks. Based on statistics analysis, we demonstrate that similar small-world networks can be constructed using Newman-Watts procedure. The network quantifiers of both structural matrices are identified inside the probabilistic valley. Despite of similarities between structural connection matrices and sampled small-world networks, increased assortat…
Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD …
In Alzheimer's disease (AD), the progressive atrophy leads to aberrant network reconfigurations both at structural and functional levels. In such network reorganization, the core and peripheral nodes appear to be crucial for the prediction of clinical outcome due to their ability to influence large-scale functional integration. However, the role of the different types of brain connectivity in such prediction still remains unclear. Using a multiplex network approach we integrated information from DWI, fMRI and MEG brain connectivity to extract an enriched description of the core-periphery struc…
The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence. However, it remains unknown whether structural brain networks are similarly refined during development, potentially allowing for improvements in executive function. In a sample of 882 participants (ages 8-22) who underwent diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that structural network modules become more segregated with age, with weaker connections between modules and stronger connections within modules. Evolving modular …
Most brain disorders including Alzheimer's disease (AD) are related to alterations in the normal brain network organization and function. Exploring these network alterations using non-invasive and easy to use technique is a topic of great interest. In this paper, we collected EEG resting-state data from AD patients and healthy control subjects. Functional connectivity between scalp EEG signals was quantified using the phase locking value (PLV) for 6 frequency bands. To assess the differences in network properties, graph-theoretical analysis was performed. AD patients showed decrease of mean co…
University of Pennsylvania（宾夕法尼亚大学）；Wu Tsai Institute, Yale University（耶鲁大学吴氏研究所）；Northeastern University（东北大学）；Ludwig-Maximilians-Universität（路德维希-马克西米利安大学）；Yale University（耶鲁大学）
It is well known that today nearly one in six of the world's population has to deal with neurodegenerative disorders. While a number of medical devices have been developed for the detection, prevention, and treatments of such disorders, some fundamentals of the progression of associated diseases are in urgent need of further clarification. In this paper, we focus on Alzheimer's disease, where it is believed that the concentration changes in amyloid-beta and tau proteins play a central role in its onset and development. A multiscale model is proposed to analyze the propagation of these concentr…
Analysis and quantification of brain structural changes, using Magnetic resonance imaging (MRI), are increasingly used to define novel biomarkers of brain pathologies, such as Alzheimer's disease (AD). Network-based models of the brain have shown that both local and global topological properties can reveal patterns of disease propagation. On the other hand, intra-subject descriptions cannot exploit the whole information context, accessible through inter-subject comparisons. To address this, we developed a novel approach, which models brain structural connectivity atrophy with a multiplex netwo…
The diagnosis of Alzheimer's disease (AD) in routine clinical practice is most commonly based on subjective clinical interpretations. Quantitative electroencephalography (QEEG) measures have been shown to reflect neurodegenerative processes in AD and might qualify as affordable and thereby widely available markers to facilitate the objectivization of AD assessment. Here, we present a novel framework combining Riemannian tangent space mapping and elastic net regression for the development of brain atrophy markers. While most AD QEEG studies are based on small sample sizes and psychological test…
McGovern Institute for Brain Research, Massachusetts Institute of Technology（麻省理工学院麦戈文脑研究所）；Complutense University of Madrid（马德里康普顿斯大学）；Harvard Medical School（哈佛医学院）
Characterizing the subtle changes of functional brain networks associated with the pathological cascade of Alzheimer's disease (AD) is important for early diagnosis and prediction of disease progression prior to clinical symptoms. We developed a new deep learning method, termed multiple graph Gaussian embedding model (MG2G), which can learn highly informative network features by mapping high-dimensional resting-state brain networks into a low-dimensional latent space. These latent distribution-based embeddings enable a quantitative characterization of subtle and heterogeneous brain connectivit…
Music, being a multifaceted stimulus evolving at multiple timescales, modulates brain function in a manifold way that encompasses not only the distinct stages of auditory perception but also higher cognitive processes like memory and appraisal. Network theory is apparently a promising approach to describe the functional reorganization of brain oscillatory dynamics during music listening. However, the music induced changes have so far been examined within the functional boundaries of isolated brain rhythms. Using naturalistic music, we detected the functional segregation patterns associated wit…
Brain-Aware Readout Layers in GNNs: Advancing Alzheimer's early Detection and Neuroimaging
AI Graduate School, Gwangju Institute of Science and Technology（光州科学技术院人工智能研究生院）；Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea（韩国天主教大学医学院首尔圣玛丽医院）；Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea（韩国天主教大学医学院汝矣岛圣玛丽医院）
Alzheimer's disease (AD) is characterized by a sequence of pathological changes, which are commonly assessed in vivo using MRI and PET. Currently, the most approaches to analyze statistical associations between brain regions rely on Pearson correlation. However, these are prone to spurious correlations arising from uninformative shared variance. Notably, there are no appropriate multivariate statistical models available that can easily integrate dozens of variables derived from such data, being able to use the additional information provided from the combination of data sources. Gaussian graph…
A whole-brain model of amyloid beta accumulation and cerebral hypoperfusion in Alzheimer's disease
Politecnico di Milano（米兰理工大学）；University of Vienna（维也纳大学）；University of Oxford（牛津大学）；Friedrich-Alexander-Universität Erlangen-Nürnberg（埃尔朗根-纽伦堡大学）；Stanford University（斯坦福大学）
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）
Cross-modal fusion of different types of neuroimaging data has shown great promise for predicting the progression of Alzheimer's Disease(AD). However, most existing methods applied in neuroimaging can not efficiently fuse the functional and structural information from multi-modal neuroimages. In this work, a novel cross-modal transformer generative adversarial network(CT-GAN) is proposed to fuse functional information contained in resting-state functional magnetic resonance imaging (rs-fMRI) and structural information contained in Diffusion Tensor Imaging (DTI). The developed bi-attention mech…
BG-GAN: Generative AI Enable Representing Brain Structure-Function Connections for Alzheimer's Disease
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）；University of Chinese Academy of Sciences（中国科学院大学）；Stevens Institute of Technology（史蒂文斯理工学院）；Hong Kong Metropolitan University（香港都会大学）；VinUniversity（越南 VinUniversity 大学）；King Fahd University of Petroleum and Minerals（法赫德国王石油矿产大学）；Uppsala University（乌普萨拉大学）；Tiangong University（天津工业大学）
Multi-Scale Graph Theoretical Analysis of Resting-State fMRI for Classification of Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
University of Bojnord（博季努尔德大学）；Munster Technological University（芒斯特理工大学）
In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed locally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) fr…
Currently, many studies of Alzheimer's disease (AD) are investigating the neurobiological factors behind the acquisition of beta-amyloid (A), pathologic tau (T), and neurodegeneration ([N]) biomarkers from neuroimages. However, a system-level mechanism of how these neuropathological burdens promote neurodegeneration and why AD exhibits characteristic progression is largely elusive. In this study, we combined the power of systems biology and network neuroscience to understand the dynamic interaction and diffusion process of AT[N] biomarkers from an unprecedented amount of longitudinal Amyloid P…
Neuroimaging biomarkers that distinguish between typical brain aging and Alzheimer's disease (AD) are valuable for determining how much each contributes to cognitive decline. Machine learning models can derive multi-variate brain change patterns related to the two processes, including the SPARE-AD (Spatial Patterns of Atrophy for Recognition of Alzheimer's Disease) and SPARE-BA (of Brain Aging) investigated herein. However, substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology toward disentangling the two. T1-we…
Northwestern University（西北大学）；Northwestern Memorial Hospital（西北纪念医院）
We propose a mesh-based technique to aid in the classification of Alzheimer's disease dementia (ADD) using mesh representations of the cortex and subcortical structures. Deep learning methods for classification tasks that utilize structural neuroimaging often require extensive learning parameters to optimize. Frequently, these approaches for automated medical diagnosis also lack visual interpretability for areas in the brain involved in making a diagnosis. This work: (a) analyzes brain shape using surface information of the cortex and subcortical structures, (b) proposes a residual learning fr…
University of Louisville（路易斯维尔大学）；University of Auckland（奥克兰大学）
Early diagnosis, playing an important role in preventing progress and treating the Alzheimer's disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposes to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capturing AD biomarkers and adapt to different domain datasets. The 3D-CNN is built upon a 3D convolutional au…
Early diagnosis, playing an important role in preventing progress and treating the Alzheimer\{'}s disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposed to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capturing AD biomarkers and adapt to different domain datasets. The 3D-CNN is built upon a 3D convolutional…
Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimer's disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuro…
To understand multifactorial conditions such as Alzheimers disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between brain circuits and cognitive markers we have used mouse models that represent, at least in part, the complex interactions altered in AD. In particular, we aimed to understand the relationship between vulnerable brain circuits and memory deficits measured in the Morris water maze, and we tested several predictive modeling approaches. We used in vivo manganese enhanced MRI voxel based ana…
University of Pennsylvania（宾夕法尼亚大学）；University of Texas San Antonio Health Science Center（德克萨斯大学圣安东尼奥健康科学中心）；National Institute on Aging（美国国家老龄化研究所）
Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy a…
Graph Neural Network Reveals the Cortical Morphology of Local Brain Aging in Normal Cognition and Alzheimer's Disease
University of Southern California（南加州大学）；University of California, Berkeley（加州大学伯克利分校）；Lawrence Berkeley National Laboratory（劳伦斯伯克利国家实验室）；King's College London（伦敦国王学院）
The Ohio State University（俄亥俄州立大学）；University of Pennsylvania（宾夕法尼亚大学）；Indiana University（印第安纳大学）
Background:Cognitive assessments represent the most common clinical routine for the diagnosis of Alzheimer's Disease (AD). Given a large number of cognitive assessment tools and time-limited office visits, it is important to determine a proper set of cognitive tests for different subjects. Most current studies create guidelines of cognitive test selection for a targeted population, but they are not customized for each individual subject. In this manuscript, we develop a machine learning paradigm enabling personalized cognitive assessments prioritization. Method: We adapt a newly developed lear…
Tri-Institutional Center for Translational Research in Neuroimaging and Data Science（三机构神经影像与数据科学转化研究中心）；Georgia State（佐治亚州立大学）；Georgia Tech（佐治亚理工学院）；Emory（埃默里大学）；Borealis AI（Borealis人工智能公司）；Mila - Quebec AI Institute（米拉-魁北克人工智能研究所）；Apple Machine Learning Research（苹果机器学习研究院）；Université de Montréal（蒙特利尔大学）
Recent neuroimaging studies that focus on predicting brain disorders via modern machine learning approaches commonly include a single modality and rely on supervised over-parameterized models.However, a single modality provides only a limited view of the highly complex brain. Critically, supervised models in clinical settings lack accurate diagnostic labels for training. Coarse labels do not capture the long-tailed spectrum of brain disorder phenotypes, which leads to a loss of generalizability of the model that makes them less useful in diagnostic settings. This work presents a novel multi-sc…
Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amy-loid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down-or up-regulation of ADAM30 expression triggered an increase/decrease in A$β$ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30 m…
Enhancing Alzheimer's Diagnosis: Leveraging Anatomical Landmarks in Graph Convolutional Neural Networks on Tetrahedral Meshes
School of Computing and Augmented Intelligence, Arizona State University, Tempe, AZ, USA（计算与增强智能学院，亚利桑那州立大学）；Amazon AGI, Redmond, WA, USA（亚马逊人工智慧部门）；Banner Alzheimer’s Institute, Phoenix, AZ, USA（贝纳尔德阿尔茨海默病研究所）
Reconstructing high-order sequence features of dynamic functional connectivity networks based on diversified covert attention patterns for Alzheimer's disease classification
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, with around 50 million patients worldwide. Accessible and non-invasive methods of diagnosing and characterising AD are therefore urgently required. Electroencephalography (EEG) fulfils these criteria and is often used when studying AD. Several features derived from EEG were shown to predict AD with high accuracy, e.g. signal complexity and synchronisation. However, the dynamics of how the brain transitions between stable states have not been properly studied in the case of AD and EEG data. Energy landscape analysis …
High-fidelity and Network-based Spatio-temporal Mathematical Models of Alzheimer's Disease Progression and their Validation Against PET-SUVR Imaging Data
Southern University of Science and Technology（南方科技大学）；Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）
Mild cognitive impairment(MCI) is a precursor of Alzheimer's disease(AD), and the detection of MCI is of great clinical significance. Analyzing the structural brain networks of patients is vital for the recognition of MCI. However, the current studies on structural brain networks are totally dependent on specific toolboxes, which is time-consuming and subjective. Few tools can obtain the structural brain networks from brain diffusion tensor images. In this work, an adversarial learning-based structural brain-network generative model(SBGM) is proposed to directly learn the structural connection…
Massachusetts General Hospital（麻省总医院）；Harvard Medical School（哈佛医学院）；University of Ferrara（费拉拉大学）
Transcranial Magnetic Stimulation (TMS) combined with EEG recordings (TMS-EEG) has shown great potential in the study of the brain and in particular of Alzheimer's Disease (AD). In this study, we propose an automatic method of determining the duration of TMS induced perturbation of the EEG signal as a potential metric reflecting the brain's functional alterations. A preliminary study is conducted in patients with Alzheimer's disease (AD). Three metrics for characterizing the strength and duration of TMS evoked EEG (TEP) activity are proposed and their potential in identifying AD patients from …
University College London（伦敦大学学院）；Indiana University（印第安纳大学）；Panakeia Technologies（Panakeia 科技公司）
Biomechanical modeling of tissue deformation can be used to simulate different scenarios of longitudinal brain evolution. In this work,we present a deep learning framework for hyper-elastic strain modelling of brain atrophy, during healthy ageing and in Alzheimer's Disease. The framework directly models the effects of age, disease status, and scan interval to regress regional patterns of atrophy, from which a strain-based model estimates deformations. This model is trained and validated using 3D structural magnetic resonance imaging data from the ADNI cohort. Results show that the framework ca…
